Engineering a 3D-Bioprinted Model of Human Heart Valve Disease Using Nanoindentation-Based Biomechanics

Nanomaterials
Dewy C van der ValkElena Aikawa

Abstract

In calcific aortic valve disease (CAVD), microcalcifications originating from nanoscale calcifying vesicles disrupt the aortic valve (AV) leaflets, which consist of three (biomechanically) distinct layers: the fibrosa, spongiosa, and ventricularis. CAVD has no pharmacotherapy and lacks in vitro models as a result of complex valvular biomechanical features surrounding resident mechanosensitive valvular interstitial cells (VICs). We measured layer-specific mechanical properties of the human AV and engineered a three-dimensional (3D)-bioprinted CAVD model that recapitulates leaflet layer biomechanics for the first time. Human AV leaflet layers were separated by microdissection, and nanoindentation determined layer-specific Young’s moduli. Methacrylated gelatin (GelMA)/methacrylated hyaluronic acid (HAMA) hydrogels were tuned to duplicate layer-specific mechanical characteristics, followed by 3D-printing with encapsulated human VICs. Hydrogels were exposed to osteogenic media (OM) to induce microcalcification, and VIC pathogenesis was assessed by near infrared or immunofluorescence microscopy. Median Young’s moduli of the AV layers were 37.1, 15.4, and 26.9 kPa (fibrosa/spongiosa/ventricularis, respectively). The fibros...Continue Reading

References

Jan 1, 1992·Journal of Biomechanics·I Vesely, R Noseworthy
Apr 4, 2003·Clinical Anatomy : Official Journal of the American Association of Clinical Anatomists & the British Association of Clinical Anatomists·Eugene K W SimCarlos Duran
Jan 11, 2005·Biomacromolecules·Jason A BurdickRobert Langer
Aug 23, 2006·Cell·Adam J EnglerDennis E Discher
Dec 23, 2006·Arteriosclerosis, Thrombosis, and Vascular Biology·David Messika-ZeitounMaurice Enriquez-Sarano
Sep 25, 2007·Journal of Biomechanical Engineering·John A Stella, Michael S Sacks
Jan 20, 2009·American Journal of Physiology. Heart and Circulatory Physiology·Kartik BalachandranAjit P Yoganathan
Mar 24, 2009·Arteriosclerosis, Thrombosis, and Vascular Biology·Cindy Ying Yin YipCraig A Simmons
Aug 12, 2009·Biomaterials·Cyrille NorotteGabor Forgacs
Nov 17, 2009·Tissue Engineering. Part a·Paul W Riem VisJolanda Kluin
Nov 17, 2009·American Journal of Physiology. Heart and Circulatory Physiology·Choon Hwai YapAjit P Yoganathan
Apr 17, 2010·Journal of Materials Research·R AkhtarB Derby
Apr 27, 2010·Biomaterials·Jason W NicholAli Khademhosseini
Jan 25, 2011·Cardiovascular Pathology : the Official Journal of the Society for Cardiovascular Pathology·Cindy Ying Yin Yip, Craig A Simmons
Aug 10, 2011·International Journal of Inflammation·Krista L SiderCraig A Simmons
Sep 28, 2012·Journal of Biomedical Materials Research. Part a·Bin DuanJonathan T Butcher
Dec 12, 2013·World Journal for Pediatric & Congenital Heart Surgery·Kai SzetoVishal Nigam
Dec 18, 2013·Biomaterials·Svenja HindererKatja Schenke-Layland
Dec 25, 2013·Beilstein Journal of Nanotechnology·Sidney R Cohen, Estelle Kalfon-Cohen
Jun 25, 2014·Advanced Healthcare Materials·Jesper HjortnaesAli Khademhosseini
Jul 8, 2014·Cardiovascular Pathology : the Official Journal of the Society for Cardiovascular Pathology·Krista L SiderCraig A Simmons
Aug 6, 2014·Nature Biotechnology·Sean V Murphy, Anthony Atala
Sep 6, 2014·Arteriosclerosis, Thrombosis, and Vascular Biology·Katherine E YutzeyElena Aikawa
Dec 10, 2014·PloS One·Stijn J A AperMaarten Merkx
Mar 22, 2016·Journal of Molecular and Cellular Cardiology·Jesper HjortnaesElena Aikawa
Jan 7, 2017·Clinical Science·Casper F T van der VenElena Aikawa
May 4, 2017·Journal of Cranio-maxillo-facial Surgery : Official Publication of the European Association for Cranio-Maxillo-Facial Surgery·Roberto L FloresLukasz Witek
Jun 18, 2017·The Annals of Thoracic Surgery·Faiz Y BhoraRobert S Lebovics

❮ Previous
Next ❯

Citations

Feb 19, 2019·Journal of Biological Engineering·Rajat VashisthaPratyoosh Shukla
Feb 12, 2020·Advanced Materials·Riccardo LevatoJos Malda
Aug 1, 2020·Small·Amin GhavamiNejadAli Khademhosseini
Jul 30, 2020·Tissue Engineering. Part a·Prashanth RavishankarKartik Balachandran
Dec 12, 2018·Nature Reviews. Cardiology·Maximillian A Rogers, Elena Aikawa
Mar 13, 2020·Arteriosclerosis, Thrombosis, and Vascular Biology·Philip Roger GoodyFelix Jansen
Jul 16, 2020·International Journal of Molecular Sciences·Gaia PedrialiPaolo Pinton
Jun 19, 2019·Journal of Ocular Pharmacology and Therapeutics : the Official Journal of the Association for Ocular Pharmacology and Therapeutics·Owen S FentonRobert Langer
Apr 8, 2020·Biofabrication·D PettaM D'Este
Apr 8, 2020·Nanoscale Horizons : the Home for Rapid Reports of Exceptional Significance in Nanoscience and Nanotechnolgy·Dean HoTheodore Kee
Oct 12, 2019·Advanced Healthcare Materials·Marleen KristenMiguel Castilho
Sep 6, 2020·International Journal of Molecular Sciences·Melania LippiElena Sommariva
Feb 13, 2021·Cardiovascular Research·Magnus Bäck, Jean-Baptiste Michel
Jan 13, 2021·Artificial Organs·Faisal QuadriSanjairaj Vijayavenkataraman
Apr 30, 2021·Circulation Research·Mark C BlaserElena Aikawa
May 28, 2021·Frontiers in Cardiovascular Medicine·Petra BüttnerFlorian Schlotter
Aug 3, 2021·Journal of Molecular and Cellular Cardiology·Ashley J ScottKristyn S Masters
Sep 11, 2021·Biofabrication·Rafaeal Hossain RakinKeekyoung Kim

❮ Previous
Next ❯

Methods Mentioned

BETA
atomic force microscopy
bioprinting
scanning-electron microscopy
bioprinter

Software Mentioned

ImageJ
Cellink
GraphPad
GraphPad Prism
- Host
R
Repetier

Related Concepts

Related Feeds

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis

Biomechanics

Biomechanics examines the generation of internal forces within the body and investigates the effects and control of forces that act on or are produced on tissues. Here are the latest discoveries.

Related Papers

Netherlands Heart Journal : Monthly Journal of the Netherlands Society of Cardiology and the Netherlands Heart Foundation
P W Riem VisJ Kluin
Nature Reviews. Cardiology
Joshua D HutchesonW David Merryman
© 2022 Meta ULC. All rights reserved